Clinical Aspects of Drug-Drug Interaction and Drug Nephrotoxicity at Renal Organic Cation Transporters 2 (OCT2) and Multidrug and Toxin Exclusion 1, and 2-K (MATE1/MATE2-K).

Abstract

The organic cation transporter 2 (OCT2) belongs to the SLC22 family, while the multidrug and toxin extrusion 1 and 2-K (MATE1/MATE2-K) belong to the SLC47 family, are localized to the basolateral and apical membrane of human renal proximal tubular epithelial cells, respectively. They are polyspecific transporters that enable the transit of structurally diversified drugs with overlapping selectivity across plasma membranes. OCT2 and MATE1/2-K are critically involved in renal secretion, pharmacokinetics (PK), and toxicity of cationic drugs. Drug-drug interactions (DDIs) at OCT2 and/or MATE1/2-K have been shown to result in clinical impacts on PK, therapeutic efficacy and are probably involved in the renal accumulation of drugs. Sites of OCT2 and MATE1/2-K expression and function play an essential role in the pharmacokinetics and toxicity of drugs, such as cisplatin. Thus, knowing the sites (basolateral vs. apical) of the interaction of two drugs at transporters is essential to understanding whether this interaction helps prevent or enhance drug-induced nephrotoxicity. In this work, an overview of OCT2 and MATE1/2-K is presented. Primary structure, membrane location, functional properties, and clinical impact of OCT2 and MATE1/2-K are presented. In addition, clinical aspects of DDIs in OCT2 and MATE1/2-K and their involvement in drug nephrotoxicity are compiled.